Our goal is to develop and apply methods suitable for preparing commercially valuable human monoclonal antibodies. In Phase I this goal will be approached by the development of an effective system for 'immortalizing' antibody secreting lymphocytes. Specifically, we will transfect human B cells with transforming DNA, obtained from different types of tumor cells, and determine the frequency of transformants which secrete antibody and grow in tissue culture. The yield of such transformants will be compared to that of human antibody secreting hybridomas obtained from cell fusion experiments using thioguanine-resistant GM1500 cells. The method found to be most effective will be used for preparing cell clones secreting antibodies to specific antigens such as enterotoxin B, cytomegalovirus, and other viral or bacterial antigens deemed to be of clinical importance. Advantage will be take of biological response modifiers, some derived from T cell hybridomas, as well as of techniques of in vitro sensitization, to increase the pool of desirable antibody secreting cells obtained from human peripheral blood.